6-(HydroxyMethyl)-2h-benzo[b][1,4]thiazin-3(4h)-one synthesis

Yield:443955-31-5 89%

Reaction Conditions:

Stage #1: 3-oxo-3,4-dihydro-2H-benzo[b][1,4]thiazine-6-carboxylic acidwith triethylamine;isobutyl chloroformate in tetrahydrofuran at 0; for 2 h;
Stage #2: with sodium tetrahydroborate in tetrahydrofuran;water at 0 - 20; for 18 h;
Stage #3: with hydrogenchloride in tetrahydrofuran;water;

Steps:

H.B 3-Oxo-3,4-dihydro-2H-benzo[1,4]thiazine-6-carbaldehyde

B. 6-Hydroxymethyl-4H-benzo[1,4]thiazin-3-one. To a 0° C. suspension of 3-oxo-3,4-dihydro-2H-benzo[1,4]thiazine-6-carboxylic acid (400 mg, 2 mmol) in THF (19 mL) was added Et₃N (0.32 mL, 2 mmol) and the resulting solution was treated with iso-butylchloroformate (0.3 mL, 2 mmol). The resulting suspension was stirred at 0° C. for 2 h, filtered and the solid was washed with THF. The filtrate was cooled to 0° C., treated with NaBH₄ (150 mg, 4.3 mmol) and slowly treated with H₂O (10 mL). The resulting suspension was, warmed to RT and stirred for 18 h. The suspension was neutralized using 1 N HCl and diluted with H₂O (100 mL). The organic layer was extracted with EtOAc (3*200 mL). The combined organic layers were dried (MgSO₄), filtered and concentrated. The resulting residue was purified on SiO₂ (0-10% CH₃OH/CH₂Cl₂) to provide 330 mg (89%) of the title compound as a white solid. MS (ESI): exact mass calculated for C₉H₉NO₂S, 195.04; m/z found, 196.1 [M+H]⁺. ¹H NMR (500 MHz, CD₃OD): 7.26 (d, J=7.9, 1H), 7.01-6.98 (m, 2H), 4.55 (s, 2H), 3.40 (s, 2H).

References:

US2006/223810,2006,A1 Location in patent:Page/Page column 22